RIII S/J mice lack an autosomal dominant gene(s) that has a decisive influence in determining the capacity to make an IgM antibody response to several representative helper T cell-independen antigens; these mice appear to possess functionally active helper T cells since they make a reasonably good antibody response to sheep erythrocytes, a helper T cell dependent antigen. Studies on the genetic defect involved, which cannot be attributed to the absence of B cells capable of giving a mitogenic response to bacterial lipopolysaccharide (LPS), may provide important new information on the genetic factors involved in antigen-induced B cell activation.